Background Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control. Objective We sought to systematically evaluate ...the efficacy and safety of systemic treatments for moderate-to-severe AD. Methods A systematic literature search was performed in MEDLINE, EMBASE, and CENTRAL (until June 2012). Randomized controlled trials (RCTs) evaluating systemic immunomodulating treatments for moderate-to-severe AD were included. Selection, data extraction, quality assessment, and generation of treatment recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed independently by 2 reviewers. Efficacy outcomes were clinical signs, symptoms, quality of life, and the course of AD. Safety data were compared by calculating the weekly incidence rates (as percentages) for adverse events. Results Thirty-four RCTs with 12 different systemic treatments and totaling 1653 patients were included. Fourteen trials consistently indicate that cyclosporin A efficaciously improves clinical signs of AD. Cyclosporin A is recommended as first-line treatment for short-term use. A second-line treatment option is azathioprine, but efficacy is lower, and evidence is weaker. Methotrexate can be considered a third-line treatment option. Recommendations are impossible for mycophenolate, montelukast, intravenous immunoglobulins, and systemic glucocorticosteroids because of limited evidence. A meta-analysis was not performed because of a lack of standardization in outcome measures. Conclusion Although 12 different interventions for moderate-to-severe AD have been studied in 34 RCTs, strong recommendations are only possible for the short-term use of cyclosporin A. Methodological limitations in the majority of trials prevent evidence-based conclusions. Large head-to-head trials evaluating long-term treatments are required.
Due to increasing demand and scarce financial resources for healthcare, health system efficiency has become a major topic in political and scientific debates. While previous studies investigating ...determinants of health system efficiency focused primarily on economic and social influence factors, the role of the political regime has been neglected. In addition, there is a lack of formal theoretical work on this specific topic, which ensures transparency and logical consistency of arguments and implications. Using a public choice approach, this paper provides a rigorous theoretical and empirical investigation of the relationships between health system efficiency and political institutions. We develop a simple principal-agent model describing the behavior of a government with respect to investments in population health under different political regimes. The main implication of the theoretical model is that governments under more democratic regimes put more effort in reducing embezzlement of health expenditure than non-democratic regimes. Accordingly, democratic countries are predicted to have more efficient health systems than non-democratic countries. We test this hypothesis based on a broad dataset including 158 countries over the period 1995-2015. The empirical results clearly support the implications of the theoretical model and withstand several robustness checks, including the use of alternative indicators for population health and democracy and estimations accounting for endogeneity. The empirical results also indicate that the effect of democracy on health system efficiency is more pronounced in countries with higher income levels. From a policy perspective, we discuss the implications of our findings in the context of health development assistance.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The European Project for Ice Coring in Antarctica Dome ice core from Dome C (EDC) has allowed for the reconstruction of atmospheric CO2 concentrations for the last 800,000 years. Here we revisit the ...oldest part of the EDC CO2 record using different air extraction methods and sections of the core. For our established cracker system, we found an analytical artifact, which increases over the deepest 200 m and reaches 10.1 ± 2.4 ppm in the oldest/deepest part. The governing mechanism is not yet fully understood, but it is related to insufficient gas extraction in combination with ice relaxation during storage and ice structure. The corrected record presented here resolves partly ‐ but not completely ‐ the issue with a different correlation between CO2 and Antarctic temperatures found in this oldest part of the records. In addition, we provide here an update of 800,000 years atmospheric CO2 history including recent studies covering the last glacial cycle.
Key Points
Analytical bias discovered in the EPICA Dome C CO2 record
Bias is confined to 13 ppm and the deepest 200 m (600–800 kyr B.P.)
Corrected and updated ice core CO2 compilation is provided
Background Clinical signs are a core outcome domain for atopic dermatitis (AD) trials. The current lack of standardization of outcome measures in AD trials hampers evidence-based communication. ...Objective We sought to provide evidence-based recommendations for the measurement of clinical signs in AD trials and to inform the Harmonising Outcome Measures for Atopic Dermatitis Initiative. Methods We conducted a systematic review on measurement properties of outcome measurements for clinical signs of AD. We systematically searched MEDLINE and Embase (until October 1, 2012) for validation studies on instruments measuring the clinical signs of AD. Grading of the truth, discrimination, and feasibility of scales; methodological study quality; and recommendations were based on predefined criteria. Results Sixteen eligible instruments were identified, of which 2 were best validated. The Eczema Area and Severity Index has adequate validity, responsiveness, internal consistency, intraobserver reliability, and intermediate interobserver reliability but unclear interpretability and feasibility. The Severity Scoring of Atopic Dermatitis Index (SCORAD) has adequate validity, responsiveness, interobserver reliability, and interpretability and unclear intraobserver reliability. Only the objective SCORAD (ie, the clinical signs domain of the SCORAD) is internally consistent. The Six Area, Six Sign Atopic Dermatitis Index severity score and Three Item Severity Score fulfill some quality criteria, but the performance in other required measurement properties is unclear. The Patient-oriented Eczema Measure is reliable and responsive but has inadequate content validity to assess clinical signs of AD. The remaining 11 scales have either (almost) not been validated or performed inadequately. Conclusions The Eczema Area and Severity Index and SCORAD are the best instruments to assess the clinical signs of AD. The other 14 instruments identified are (currently) not recommended because of unclear or inadequate measurement properties.
There are a few epidemiological studies that (1) link increased ambient air pollution (AP) with an increase in lung cancer incidence rates and (2) investigate whether residing in green spaces could ...be protective against cancer. However, it is completely unclear whether other forms of cancer are also affected by AP and if residential green spaces could lower cancer incidence rates in general. Therefore, the objective was to estimate whether AP and green space are associated with several cancer types.
The analysis was based on routine health care data from around 1.9 million people from Saxony who were free of cancer in 2008 and 2009. Incident cancer cases (2010-2014) of mouth and throat, skin (non-melanoma skin cancer - NMSC), prostate, breast, and colorectum were defined as: (1) one inpatient diagnosis, or (2) two outpatient diagnoses in two different quarters within one year and a specific treatment or death within two quarters after the diagnosis. Exposures, derived from freely available 3rd party data, included particulate matter with aerodynamic diameter of less than 10 μm (PM
) and nitrogen dioxide (N0
) as well as green space (Normalized Difference Vegetation Index - NDVI). Associations between air pollutants, green space, and cancer incidence were assessed by multilevel Poisson models. Age, sex, physician contacts, short- and long-term unemployment, population density, and having an alcohol-related disorder were considered as potential confounders.
Three thousand one hundred seven people developed mouth and throat cancer, 33,178 NMSC, 9611 prostate cancer, 9577 breast cancer, and 11,975 colorectal cancer during the follow-up period (2010-2014). An increase in PM
of 10 μg/m
was associated with a 53% increase in relative risk (RR) of mouth and throat cancer and a 52% increase in RR of NMSC. Prostate and breast cancer were modestly associated with PM
with an increase in RR of 23 and 19%, respectively. The associations with N0
were in the same direction as PM
but the effect estimates were much lower (7-24%). A 10% increase in NDVI was most protective of mouth and throat cancer (- 11% RR) and of NMSC (- 16% RR). Colorectal cancer was not affected by any of the exposures.
In addition to the studies carried out so far, this study was able to provide evidence that higher ambient AP levels increase the risk of mouth and throat cancer as well as of NMSC and that a higher residential green space level might have a protective effect for NMSC in areas with low to moderate UV intensity. Nevertheless, we cannot rule out residual confounding by socioeconomic or smoking status.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Core outcome sets (COS) can enhance the relevance of research by ensuring that outcomes of importance to health service users and other people making choices about health care in a particular topic ...area are measured routinely. Over 200 COS to date have been developed, but the clarity of these reports is suboptimal. COS studies will not achieve their goal if reports of COS are not complete and transparent.
In recognition of these issues, an international group that included experienced COS developers, methodologists, journal editors, potential users of COS (clinical trialists, systematic reviewers, and clinical guideline developers), and patient representatives developed the Core Outcome Set-STAndards for Reporting (COS-STAR) Statement as a reporting guideline for COS studies. The developmental process consisted of an initial reporting item generation stage and a two-round Delphi survey involving nearly 200 participants representing key stakeholder groups, followed by a consensus meeting. The COS-STAR Statement consists of a checklist of 18 items considered essential for transparent and complete reporting in all COS studies. The checklist items focus on the introduction, methods, results, and discussion section of a manuscript describing the development of a particular COS. A limitation of the COS-STAR Statement is that it was developed without representative views of low- and middle-income countries. COS have equal relevance to studies conducted in these areas, and, subsequently, this guideline may need to evolve over time to encompass any additional challenges from developing COS in these areas.
With many ongoing COS studies underway, the COS-STAR Statement should be a helpful resource to improve the reporting of COS studies for the benefit of all COS users.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The standardized mortality ratio (SMR) is often used to assess and compare hospital performance. While it has been recognized that hospitals may differ in their SMRs due to differences in patient ...composition, there is a lack of rigorous analysis of this and other-largely unrecognized-properties of the SMR. This paper proposes five axiomatic requirements for adequate standardized mortality measures: strict monotonicity (monotone relation to actual mortality rates), case-mix insensitivity (independence of patient composition), scale insensitivity (independence of hospital size), equivalence principle (equal rating of hospitals with equal actual mortality rates in all patient groups), and dominance principle (better rating of unambiguously better performing hospitals). Given these axiomatic requirements, effects of variations in patient composition, hospital size, and actual and expected mortality rates on the SMR were examined using basic algebra and calculus. In this regard, we distinguished between standardization using expected mortality rates derived from a different dataset (external standardization) and standardization based on a dataset including the considered hospitals (internal standardization). The results were illustrated by hypothetical examples. Under external standardization, the SMR fulfills the axiomatic requirements of strict monotonicity and scale insensitivity but violates the requirement of case-mix insensitivity, the equivalence principle, and the dominance principle. All axiomatic requirements not fulfilled under external standardization are also not fulfilled under internal standardization. In addition, the SMR under internal standardization is scale sensitive and violates the axiomatic requirement of strict monotonicity. The SMR fulfills only two (none) out of the five proposed axiomatic requirements under external (internal) standardization. Generally, the SMRs of hospitals are differently affected by variations in case mix and actual and expected mortality rates unless the hospitals are identical in these characteristics. These properties hamper valid assessment and comparison of hospital performance based on the SMR.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COMET Handbook: version 1.0 Williamson, Paula R; Altman, Douglas G; Bagley, Heather ...
Current controlled trials in cardiovascular medicine,
06/2017, Letnik:
18, Številka:
Suppl 3
Journal Article
Recenzirano
Odprti dostop
The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, ...the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified.
Background Valid and reliable outcome measurements are a prerequisite for evidence-based practice. The comparative validity and reliability of outcome measurements for assessing atopic eczema (AE) ...severity is unclear. Objective We sought to assess the validity, reliability, sensitivity to change, and ease of use of outcome measurements for AE. We also sought to give recommendations on which outcomes to use in clinical research and for clinical monitoring. Methods We performed a systematic review and survey of clinical experts and patients. Results Twenty published outcome measurements were identified. There is evidence of adequate construct validity for 3 measurements (Severity Scoring of Atopic Dermatitis index SCORAD, Eczema Area and Severity Index EASI, and Three Item Severity Score), adequate internal consistency of 1 scale (Patient-oriented Eczema Measure POEM), adequate interobserver reliability of 5 measurements (Basic Clinical Scoring System; Nottingham Eczema Severity Score; Objective Severity Assessment of Atopic Dermatitis; Six Area, Six Sign Atopic Dermatitis severity score; and SCORAD), adequate test-retest reliability of 1 scale (POEM), and adequate sensitivity to change of 3 measurements (EASI, SCORAD, and Investigators' Global Atopic Dermatitis Assessment). Most outcome measurements have adequate content validity, as assessed by patients and experts. Data on the time to perform the assessment was identified for 8 outcome measurements. Only SCORAD, EASI, and POEM have been tested sufficiently and performed adequately. Conclusion There are too many published outcome measures for AE. Most have not been tested properly or perform adequately when tested, and their continued use hampers scientific communication. Clinical implications Only SCORAD, EASI, and POEM currently perform adequately. These scales should be used in future studies.
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